1. Field of the Invention
Embodiments of the present invention relate generally to sample disrupters such as ball mills (also called bead mills). More particularly, representative embodiments concern the use of irregular disrupting particles, instead of standard balls, that more effectively disrupt samples.
2. Description of Related Art
For a number of applications, the need has arisen for hands-off disruption of samples such as biological samples. In particular, there is a need to disrupt gram-sized biological samples. This need is particularly acute for molecular diagnostics using clinical specimens. Historically, samples in this size range have been processed by mortar and pestle followed by homogenization using a rotor-stator device (polytron) followed by purification by organic extraction or on a glass filter.
Several vendors currently sell closed-tube tissue disrupter systems in which disruption of a sample is achieved by agitating the sample in a lysis buffer in the presence of a disrupting media. This media is typically 1-2.5 mm spherical balls or beads made of stainless steel, zirconium, or other dense material. Advantages for this “closed system” approach include: (a) no release of irritating or toxi aerosols; (b) fast processing (˜2 to 4 minutes); (c) less potential for sample to sample cross-contamination; (d) ease of operation; (f) relatively maintenance free; (g) easy use in a clinical setting; and (h) potentially disposable.
Example commercial products include the MIXER MILL MM 300 by QIAGEN, the FASTPREP instrument by QBIOGENE, and the MINIBEADBEATER by BioSpec.
Although these commercial products work well and can produce, e.g., high-quality RNA from biological samples, drawbacks nevertheless exist. First, commercial machines capable of homogenizing large samples can be relatively expensive. Second, the total amount of biological sample that can be efficiently disrupted using these machines is limited (e.g., it is believed that the amount is currently about 30 mg for the commercial MM 300 device to about 300 mg for the commercial FASTPREP device). Third, commercially-available disrupters often take too long to disrupt samples and particularly relatively large samples. Depending on the type of sample being disrupted, this may not be a major concern. However, if the sample being disrupted is a biological sample, it is beneficial to achieve the most efficient, rapid disruption possible. To isolate biological materials, a cell structure typically has to be destroyed. This lysis should be accomplished very rapidly, if possible, in the most efficient manner possible because nucleic acids (particularly RNA) can degrade rapidly after the destruction of a cell structure.
The referenced shortcomings of conventional methodologies mentioned above are not intended to be exhaustive, but rather are among many that tend to impair the effectiveness of previously known techniques concerning disrupters. Other noteworthy problems may also exist; however, those mentioned here are sufficient to demonstrate that methodology appearing in the art has not been altogether satisfactory and that a significant need exists for the techniques described and claimed here.